environmental toxicology and pharmacology 32 ( 2 0 1 1 ) 349–355 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/etap Additive effect of dl-penicillamine plus Prussian blue for the antidotal treatment of thallotoxicosis in rats Sergio Montes a , Gabriela Pérez-Barrón b , Moisés Rubio-Osornio c , Camilo Ríos a,d , Araceli Diaz-Ruíz a , Marina Altagracia-Martínez d , Antonio Monroy-Noyola b,∗ a Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, “Manuel Velazco Suárez”, SS, Av. Insurgentes Sur No. 3877, C.P. 14269, México, D.F., México b Laboratorio de Neuroprotección, Facultad de Farmacia. Universidad Autónoma del Estado de Morelos, Av. Universidad 1001 Col. Chamilpa, C.P. 62209, Cuernavaca, Morelos, México c Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, “Manuel Velazco Suárez”, SS, Av. Insurgentes Sur No. 3877, C.P. 14269, México, D.F., México d Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, México, D.F., México article info Article history: Received 12 February 2011 Received in revised form 22 June 2011 Accepted 6 July 2011 Available online 27 July 2011 Keywords: Thallium Thallium antidotes dl-Penicillamine Prussian blue Brain abstract dl-penicillamine (DL-P) and Prussian blue (PB) given alone or in combination were tested as possible treatments against acute thallium toxicity. Rats were intoxicated by i.p. injec- tion of thallium (I) acetate at LD 50 (32 mg/kg). A day later, pharmacological treatment was administered until day 4 as follows: (1) vehicles, (2) PB 50mg/kg, by oral route, twice a day, (3) DL-P 25mg/kg i.p. route, twice daily and (4) PB+DL-P. The Estimated Probability Survival (EPS) was recorded during the experiment for each treatment. DL-P alone did not show a sig- nificant effect on survival. However, when it was used in combination with PB, it increased the survival significantly (EPS = 0.8, P < 0.05) as compared to the control group (EPS = 0.4). In a different experiment, using 16 mg/kg of Thallium I acetate, the metal levels were analyzed in blood, body organs and brain regions after treatments. DL-P given alone decreased slightly the thallium content in blood, organs and brain. Meanwhile, its administration in combina- tion with PB diminished the thallium levels significantly (P < 0.05) in the majority of tissues, at levels lower than those achieved in the PB group. Those results indicate that DL-P admin- istered alone did not prevent the mortality nor accumulation of the metal in body tissues. Its combination with PB could be considered an alternative antidotal treatment in thallium toxicity, because this chelating agent given alone did not cause thallium redistribution to the brain. When given in combination with PB it has an additive effect in the treatment of acute thallotoxicosis. © 2011 Elsevier B.V. All rights reserved. Abbreviations: DL-P, dl-penicillamine; PB, Prussian blue; EPS, estimated probability of survival. ∗ Corresponding author. Tel.: +52 777 329 70 89x7122; fax: +52 777 329 79 89. E-mail address: amonroy@uaem.mx (A. Monroy-Noyola). 1382-6689/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2011.07.002